髓系抑制性细胞（MDSC）是肿瘤免疫耐受的重要参与者，但肿瘤中MDSC聚集及活化的调控机制尚待阐明。我们前期研究发现肿瘤来源PMN-MDSC中BATF2表达水平降低，敲除BATF2可促进PMN-MDSC聚集及活化，促进肿瘤生长；过表达BATF2可抑制MDSC产生，下降MDSC关键基因S100A9的表达。因而我们提出“BATF2通过转录抑制S100A9，从而抑制肿瘤中PMN-MDSC聚集、活化，进而抑制肿瘤生长”的科学假说。本项目拟从以下方面进行验证：研究BATF2对肿瘤中PMN-MDSC的调控作用；以S100A9为主要对象，研究BATF2调控PMN-MDSC的分子机制；探明BATF2调控PMN-MDSC对肿瘤生长及转移的影响；最后利用临床肿瘤样品分析BATF2表达与PMN-MDSC水平及病程进展之间的相关性。本项目的实施将揭示调控肿瘤中PMN-MDSC的新机制，为肿瘤免疫治疗提供新靶点。

Myeloid deprived suppressor cell (MDSC) plays a critical role in immune suppression of malignancies. However, its intracellular molecular regulation pathway is still not clear. In our preliminary study, we found decreased expression of BATF2 in tumor induced polymorphonuclear cell MDSC (PMN-MDSC). BATF2 knock out (KO) promoted PMN-MDSC accumulation and activation in tumor bearing BATF2-KO mice, as well as tumor growth. Over expression of BATF2 reduced MDSC and S100A9 expression in MDSC, which was critical for MDSC development. Thus, we speculated that BATF2 suppressed tumor progression through regulation of PMN-MDSC differentiation via transcriptional suppression of S100A9.In the preset project, we will further confirm the presumption with following experiments. Firstly, the influence of BATF2 on PMN-MDSC in tumor will be investigated. Then, based on S100A9, the molecular mechanism in this biological process would be clearly mapped. Furthermore, the role of BATF2 in tumor growth and metastasis would be determined in tumor bearing mice modes. Finally, the association between BATF2 and PMN-MDSC as well as disease progression would be tested by study based on clinical samples. Our project will provide a novel regulatory mechanism in malignancy related PMN-MDSC, which would provide a new target for anti-cancer immunotherapy.